Livestock products with an increased ppar/rxr heterodimer activator level

ABSTRACT

In the non-therapeutic method livestock animals, used in agri- or aquaculture for producing livestock products, are made to ingest at least one product comprising a PPAR/RXR heterodimer activator and/or a precursor thereof over such a period of time and in such an amount that the PPAR/RXR heterodimer activator is accumulated in the livestock animal. In this way, livestock products such as meat, milk and eggs having an increased PPAR/RXR heterodimer activator level can be obtained. The PPAR/RXR heterodimer activator is phytanic acid, a metabolite of phytanic acid, a derivative of phytanic acid or of said metabolite, or a combination thereof. In order to accumulate the PPAR/RXR heterodimer activator in the livestock animal, a predetermined minimum amount of said product, in particular of phytol, is given to the livestock animals over at least one period of at least three days.

The present invention relates to a non-therapeutic method for achievingan increased level of at least one PPAR/RXR heterodimer activator in alivestock product for human consumption, in particular in skeletal meat,milk and/or eggs, in which method livestock animals, used in agri- oraquaculture for producing the livestock product, are made to ingest atleast one product comprising said PPAR/RXR heterodimer activator and/ora precursor thereof which is metabolised by the livestock animals intosaid PPAR/RXR heterodimer activator, over such a period of time and insuch an amount that the PPAR/RXR heterodimer activator is accumulated inthe livestock animal so that said increased PPAR/RXR heterodimeractivator level is achieved in the livestock product.

An example of a PPAR/RXR heterodimer activator is conjugated linoleicacid (CLA). EP-A-1 106 077 discloses a method wherein a feed comprisingextruded linseed is given to cows. This feed is intended to achieve milkhaving a particular content of saturated and unsaturated fatty acidsand, in particular, an elevated CLA content. Other methods wherein thelevel of CLA in ruminant livestock products is enhanced through alteringthe dietary composition in the feeds such that more CLA is produced aredisclosed in [Offer 1998] and in [Chilliard 2000]. CLA can also besupplemented directly to the feeds of other livestock such as pigs[Ostrowska 1999], poultry and fish in order to achieve enhanced levelsof CLA in pork, chicken meat, eggs and fish meat.

In the following table, a number of references disclosing CLA levelsobtained by supplementing the feed of livestock animals with CLA aregiven. It displays per reference, the product targeted, the maximumlevel of CLA in the diet by weight and the maximum level of CLA found inthat product as a percent of total fatty acids. max in Reference productdiet max of TFA Chamruspollert egg yolk 5% 11.2%  1999 Shafer 2001 eggyolk 2% 7.95%  Raes 2002 egg yolk 3% 5.3% Szymczyk 2001 Chicken meat1.5%   10.27%  Choi 1999 Carp 1%  13% Twibell 2000 striped bass 0.6%  8.1% Twibell 2001 yellow perch 0.6%   2.92%  Ramsey 2001 lean pork1.4%   3.2% (up to 55 kg) Thiel-Cooper lean pork 1% 0.7% 2001 (>100 kg)Joo 2002 lean pork 5% 1.6% (>100 kg)

CLA is a fatty acid that has generated a lot of interest with respect tohealth since the discovery that grilled minced beef could inhibitcarcinogenesis [Ha 1987]. During the last 15 years, numerous otherphysiological properties have been attributed to CLA beside it beinganticarcinogenic [Belury 2002], including action as an antiadipogenic[Smedman 2001], antidiabetogenic [Houseknecht 1998, Ryder 2001] andantiatherosclerotic [Wilson 2000] agent. Furthermore CLA has effects onbone formation [Li 1999] and the immune system [Sugano 1998].

CLA stands for a group of positional and stereo-isomers of conjugatedoctadecadienoic acid, a fatty acid doubly unsaturated in positionsseparated by just one single bound and whereby one of the double boundsis in trans and the other in the cis steomeric configuration.

The natural source of CLA in foods is almost exclusively from ruminantlivestock products like beef, lamb and dairy. The predominant isomer isc9t11-CLA. Several other isomers are also found such as t7,c9-CLA,c11t13-CLA, c8t10-CLA and t10c12-CLA [Fritsche 1999].

The synthetic production of CLA is usually based on an alkalinisation ofa linoleic acid substrate. This process generates predominantly twoisomers in roughly equal proportions: c9t11-CLA and t10c12-CLA [Reaney1999]. The majority of the studies on CLA were performed with such a CLAisomer mixture.

In the general population, the intake of CLA has been estimated to varywidely between 15-659 mg/day [Park 1999]. As amounts as small as 0.5% ofdiet have been shown to alter expression of genes and impact conditionssuch as carcinogenesis, obesity, diabetes, and atherosclerosis in,mostly, animal studies, it is quite likely that these amounts taken overlonger periods have similar benefits for the specific human subgroups.

The mechanisms underlying the beneficial effects of CLA are slowly butsurely being elucidated. One complicating factor is that the differentCLA isomers seem to have some common and some different courses ofaction [Pariza 2001].

One line of action is based on the mediation of the peroxisomeproliferator-activated receptor (PPAR). These are orphan nuclearreceptors that require a dimerisation with a retinoid-X receptor (RXR)that when activated, straddle the peroxisome proliferator responseelements (PPRE's) on the DNA to trigger the transcription of aparticular set of genes. PPARs come in three families alpha, beta (ordelta) and gamma.

PPAR alpha is a PPAR family that is involved in the metabolism of fattyacids and lipoproteins. Synthetic activators of PPAR alpha include thelipid-lowering fibrates. These have been used for years in clinicalmedicine to treat dyslipidemias. In addition, PPAR alpha activationimproves insulin sensitivity and decreases inflammation in the vascularwalls and thrombi. Each of these is an important factor in the onset,progression and complications of atherosclerosis. Furthermore, PPARalpha ligands have been shown to prevent the induction and halt theprogression of certain cancers in cell line and animal models. It hasbeen shown that CLA is an agonist of PPAR alpha [Moya-Camarena 1999].

PPAR gamma is another PPAR family that is involved with adipogenesis andlipid metabolism. Thiazolidinediones (TZD) are potent insulinsensitizers used to treat type II diabetes. They were found to besynthetic ligands of PPAR gamma. In addition, PPAR gamma stimulationinhibits the production of a number of cytokines that are involved inpromoting inflammation. Furthermore, the activation of PPAR gamma hasbeen shown to prevent the induction of a number of cancers by promotingcell differentiation and stimulating apoptosis. It has been shownconclusively that CLA is an agonist of PPAR gamma [Houseknecht 1998, Yu2002].

A second mode of action is through the inhibition of particular enzymesthat elongate [Chuang 2001] and desaturate [Park 2000] fatty acids.Although the impact of a mix of isomers of CLA, or of the individualisomers are not fully elucidated yet, it appears that CLA, through thismechanism, influences the level and character of cytokines derived fromthe LOX and COX fatty acid oxidation pathways [Urquhart 2002] and,consequently, impacts inflammation and blood clotting behavior.

Given the important potential health benefits of CLA, the required dailyallowance has been calculated to be between 1.5 g and 3 g per day[Decker 1995]. As the present level of CLA in the diet is about three toten times less than required, it became necessary to devise ways tosupplement CLA in the human diet.

Although CLA is a compound with a unique position in the human foodchain and with interesting properties and potential for healthpromotion, it presents a number of important hurdles for its generalizedsupplementation in the human diet:

CLA is represented by a variety of isomers exposing different andsometimes even opposite activities.

The mechanisms of action of CLA are varied and influencing severaldifferent pathways simultaneously making it hard to elucidate therelative importance of each.

As CLA joins the same pathways as linoleic acid and linoleic acid is akey-precursor for a couple of families of cytokines involved in thedelicate balance in inflammation and clotting, the effect of CLA derivedcytokines on this balance is worrisome.

CLA supplementation decreases to a certain degree the effect ofendogenous desaturases [Lee 1998]. This causes a serious shift in thefatty acid profile of foods from animal origin towards more of the lessdesirable saturated fatty acids.

The large majority of studies have been using a mix of CLA isomers,complicating the interpretation of the mechanisms of action even moreand casting serious doubt on any extrapolation.

CLA is an unsaturated fatty acid and thus prone to oxidation [Hamalainen2002], for example during cooking. Although CLA is relatively stableduring storage and processing, the toxicological profile of itsdegradation products in foods remains elusive. In vivo, CLA has beenshown to be reactive enough to, at least, induce lipid peroxidationproducts that are markers of arteriosclerosis [Basu 2000, Riserus 2002].

The natural sources of CLA in the food chain are bacteria detoxifying alinoleic acid overload [Fukuda 2002]. The complete chemical synthesis ofCLA is possible but not well established. The industrial production ofCLA from plant based oils generates an unnatural mix of isomers [Saebo2001]. Moreover, the isomer specific purification of CLA is far fromtrivial.

In addition, it has been shown that CLA is produced endogenously fromthe trans monoene vaccenic acid [Adlof 2000] [Loor 2002]. This puts intoquestion the necessity to supplement foods with CLA, in particular withisomers that are not generated by the mammalian organism itself.

Furthermore, the association between CLA and a trans fatty acid likevaccenic acid complicates the interpretation of the conflict between thepotential beneficial effects of CLA and the generally accepted noxiouseffects of trans fatty acids.

Lastly, upto now there is little data about the effect of CLA in acutetoxic and long-term lower level overload conditions.

An object of the present invention is to provide a new method forproducing livestock products for human consumption which enables toachieve livestock products which also have interesting properties andpotential for health promotion due to the presence of an increased levelof a PPAR/RXR heterodimer activator but wherein a PPAR/RXR heterodimeractivator or a precursor thereof different from CLA is used so that atleast a number of the drawbacks of CLA indicated hereabove are obviated.

To this end, the method according to the present invention ischaracterised in that said PPAR/RXR heterodimer activator is phytanicacid, a metabolite of phytanic acid, a derivative of phytanic acid or ofsaid metabolite, or a combination thereof and, in order to accumulatethe PPAR/RXR heterodimer activator in the livestock animal, apredetermined amount of said product is given to the livestock animalsover at least one period of at least three days, during which thelivestock animals ingest a total amount of F kg feed dry weight, whichpredetermined amount of said product contains at least 5×F meq,preferably at least 10×F meq, and more preferably at least 15×F meq ofsaid PPAR/RXR heterodimer activator and/or precursor thereof.

Phytanic acid (PhA) is the common name for tetramethylhexadecanoic acid,a saturated fatty acid with four methyl branches. The PhA catabolism hasbeen studied extensively for the last forty years, primarily, to explainthe pathophysiology of Refsum's disease, a rare genetic disorderaffecting the peroxisome metabolism [Verhoeven 2001]. In the lateseventies, it was found that adhering to a low PhA diet could preventthe noxious accumulation of PhA and, soon, the PhA levels of foodstuffswere measured and specific dietary tables were established[Masters-Thomas 1980].

In the human diet, the most important sources of PhA are rumen products,such as from beef and dairy products, and fish products such as fromherring, sardines and mackerel and the like. The PhA in these animals isthe result of the uptake of phytol released during the breakdown ofchlorophyll. Phytol is converted to PhA in the liver. PhA itself isbroken down in pristanic acid (PrA) through an alpha-oxidation andsubsequently in trimethyltetradecanoic acid (TMTD) through abeta-oxidation. Both these oxidations and the following twobeta-oxidations occur in the peroxisome. The next ones occur in themitochondrium.

In the rumen of ruminants, the chlorophyll contained in the foragegrasses is broken down during the fermentation in the gut. The fish, onthe other hand, obtain phytol by ingesting zooplankton that has beenfeeding on the phytoplankton. It is not generally known whichmicroorganisms are responsible for hydrolyzing chlorophyll, neither inthe rumen nor in the plankton.

After [Van den Branden 1986] noted that dietary phytol induced theproliferation of hepatic peroxisomes in adult mice, cell research showedthat PhA is a ligand of RXR [Kitareewan 1996] and subsequently it wasidentified as a potent activator of PPAR alpha in physiologicconcentrations [Ellinghaus 1999]. These characteristics point towards anumber of promising human health claims such as against atherosclerosis[Pineda Torra 1999], non-insulin dependent diabetes [Lenhard 2001] andcancer [Roberts-Thomson 2000]. As CLA had also been found to be anagonist of PPAR alpha [Moya-Camarena 1999] and PPAR gamma [Houseknecht1998], some potential health benefits of CLA were hypothesized topertain also to PhA.

In 2001, McCarty hypothesised that supplementing the human diet withhydrolysed chlorophyll at a dosage of 0.5% of the diet weight in freephytol could be an effective prevention and treatment of non-insulindependent diabetes [McCarty 2001]. He based his argument on the findingthat cell research showed that some early phytol metabolites are aligand of RXR [Kitareewan 1996] and that the PPARgamma/RXR heterodimerwas suggested as a target for treating diabetes [Mukherjee 1997]. As CLAwas found to be an agonist of PPAR gamma [Houseknecht 1998], some healthbenefit claims of CLA could possibly extend also to phytol and itsmetabolites.

Although the potential beneficial effects of PhA are known and althoughdirect supplementation of the human diet with PhA or its precursorphytol has already been disclosed in [McCarty 2001], EP-A-1 177 789 andin WO-A-9709039, nobody has suggested up to the present invention anyfeeding strategy to enhance the level of phytol or its metabolites orderivatives thereof in food products of animal origin for humanconsumption.

Compared to the above described disadvantages of the prior art methodswherein the human food is supplemented with CLA, the method according tothe invention offers however the following advantages as a result of theuse of PhA (or metabolites or derivatives thereof) as PPAR/RXRheterodimer activator:

As PhA is completely saturated it does not present itself in differentisomeric configurations, exposing possibly different activities like CLAisomers do.

Although it cannot be excluded that PhA has other more subtle mechanismsof action, its main effect is evidently through its agonistic effect onthe PPAR/RXR system.

Although it cannot be excluded that PhA metabolises in other minorpathways, its main catabolic pathway has been completely elucidated inminute detail, together with a list of known genetic mutations thatperturb this pathway.

Although only relatively few PhA supplementation studies have beenperformed, their interpretation is not complicated by a mixture ofcompounds with possible opposing activities like with CLA.

As PHA is fully saturated there is no inherent problem of oxidation.This means that the compound is not only stable during storage,processing and heating, but that also we do not expect in vivo reactionssuch as lipid peroxidation that cast doubt over CLA as a potentialhealthy supplement.

The natural source of PhA is the chlorophyll used in plants and algae.The complete synthetic chemical synthesis is well established [Eldjarn1966] and is the preferred industrial method to produce precursors ofvitamins such a vitamin K and vitamin E. The industrial production ofPhA from plant-based material is also relatively trivial.

As there is no endogenous production of PhA from any lower levelprecursor in the animal kingdom, all PhA in the organism is of dietaryorigin. This eliminates the uncertainty about influences of otherprecursors like trans vaccenic acid does with in CLA studies.

As Refsum patients have been studied thoroughly, we have extensiveinformation about the metabolic effects of long term toxic doses.

Direct supplementation of the human or animal diet with phytol orphytanic acid has already been disclosed in the prior art but only fortherapeutic purposes. EP-A-1 177 789 discloses the therapeutic use ofPhA or phytol for the treatment or prevention of diabetes whilst inWO-A-9709039, PhA is described to be a vitamin, more particularlyvitamin F, which can be used for treating vitamin F deficiency. Vitaminsare however used in very small, trace concentrations and are never meantto accumulate in tissues. Moreover, also in EP-A-1 177 789, the phytanicacid or phytol is administered in relatively small daily doses, moreparticularly in daily doses of between 0.1 and 50 mg/kg body weight, andusually of between 0.5 and 40 mg/kg body weight. Although EP-A-1 177 789mentions the use of phytol or phytanic acid for preventing or treatingdiabetes in humans or animals, it does not teach any specific animalsand a skilled person would not use it for livestock animals since theseanimals do not suffer from diabetes that warrants treatment. Moreover,EP-A-1 177 789 does not teach to supplement feed with phytol or phytanicacid to achieve an accumulation of phytanic acid in the livestockproducts, no tissue concentrations being indicated at all.

In other prior art documents, the accumulation of PhA in certain tissueshas been mentioned.

Lough [Lough 1977] has noted the possible effect of natural feeds(containing chlorophyll) on the level of PhA in the liver, kidney,heart, brain, omental fat, plasma and milk in a dozen of cows and steersHowever, this method is not in accordance with the present inventionsince the grass silage fed in these experiments contained only arelatively small amount of chlorophyll. Moreover, chlorophyll can onlybe broken down in ruminants so that feeding chlorophyll to non-ruminantswill have no significant effect on the PhA content.

In contrast to chlorophyll, phytol can be metabolised in non-ruminants.In the prior art, only laboratory animals have, however, beensupplemented with phytol, primarily to elucidate the pathophysiology ofRefsum's disease. In general, it was moreover noted that substantialmorbidity as evidenced by growth retardation, weight loss and lethargy,already emerged from levels of supplementation of 1% of diet weight onand serious mortality rates were induced at levels of 5% [Steinberg1966].

From the prior art it thus appears that phytol supplementation has suchtoxic effects on growth and health in laboratory animals that [Steinberg1966] concluded, albeit within the context of the development of ananimal model for Refsum's disease, that “the dosages of dietary phytolor phytanic acid needed to produce tissue accumulation of phytanic acidin normal animals are large and incompatible with growth and survival inthe species tested.”

According to the invention it was found that, under standard zootechnical conditions, it appeared to be possible to achieve increasedlevels of PhA (or metabolites or derivatives thereof) in livestockproducts by supplementing the feed of livestock animals with phytol orother compounds forming or producing the above described PPAR/RXRheterodimer activator, more particularly, increased levels that have abeneficial effect on the health of the humans consuming the livestockproducts. This is quite surprising not only in view of the toxic effectsof phytol but also in view of the fact that the branched nature of PhAseriously impedes the activity of several fatty acid enzymes that do notseem impacted as much by CLA. As indirect evidence, it was already notedthat the presence of PhA in substantial proportion in the triglyceridesand phospholipids was associated with the presence of phytenic acid (andnot PhA) in the cholesterol esters of plasma [Steinberg 1966] but notwith its deposition in quantity in a series of tissues. For example, PhAapparently inhibits the adipose tissue lipoprotein lipase, blocking itssignificant deposition in fat tissue. Also the mamary gland lipoproteinlipase discriminates against PhA, severely limiting the deposition ofPhA in the milk, despite high plasma levels. Illustrative is also thatthe placental barrier is virtually impermeable to PhA [Lough 1977].

Consequently, one cannot extrapolate the deposition rate of PhA in theegg, for example, nor in the skeletal muscle of the growing organism.Granted, the deposition of PhA in the heart of grass fed steers wassignificant [Lough 1977]. Indeed, as the heart muscle is constantlyactive, it has an excessive and continuous energy requirement incontrast to other muscle types. As most of the energy is provided byfatty acids, the heart muscle has a very high turn over rate of itsfatty acids. Consequently, dietary changes are more readily reflected inthe fatty acid profile of the heart muscle, even if a particularcompound, like PhA, is far from being the preferred substrate. However,skeletal muscles have much lower energy requirements and their mainenergy source is glycogen, not fatty acids. Therefore, the turn overrate of fatty acids in skeletal muscle is manyfold lower than that forthe heart muscle and their metabolic enzymes are under a substantiallydifferent tissue specific control and configuration.

In the method according to the invention, the human diet is supplementedwith a PPAR/RXR heterodimer activator in order to achieve beneficialhealth effects. The PPAR/RXR dimer activator is an agonist of any of thePPARs alpha and gamma and/or of the RXR enabling to activate thePPAR/RXR dimer so that it may straddle the peroxisome proliferatorresponse elements (PPRE) on the DNA to trigger the transcription of aparticular set of genes. The PPAR/RXR heterodimer activator employed inthe present invention is phytanic acid, a metabolite of phytanic acid, aderivative of phytanic acid or of said metabolite, or a combinationthereof. The PPAR/RXR heterodimer activator is advantageously phytanicacid, pristanic acid, TMTD (4,8,12trimethyltridecanoic acid), aderivative of these acids or a combination thereof, the PPAR/RXRheterodimer activator being preferably phytanic acid and/or pristanicacid.

In the method according to the invention, the level of one or more ofthese PPAR/RXR heterodimer activators is increased in livestockproducts, in particular in skeletal meat, milk and/or eggs, produced bylivestock animals in agri- or aquaculture. This is achieved by makingthe livestock animals ingest at least one product that comprises thePPAR/RXR heterodimer activator and/or a precursor thereof, which ismetabolised by the livestock animals into the PPAR/RXR heterodimeractivator. The product can be in the form of a feed or a feed supplementfed to the animals (either via the feed or via the drinking fluids). Animportant advantage of the method according to the invention is that, byfeeding the product to livestock animals instead of directly to humans,the human food itself is rendered more healthy but with at least oneorder of magnitude lower risk of overload, overdoses or adverse effectsfor the consumers.

When the livestock animals are ruminants, chlorofyll can be given asprecursor of the PPAR/RXR heterodimer activator. This chlorophyll ispreferably contained in a chlorophyll rich product containing at least0.25% by dry weight, preferably of at least 0.50% by dry weight and morepreferably of at least 0.75% by dry weight chlorophyll. Examples of suchchlorophyll rich products are chlorophyll paste, Chlorella powder, driedblue green algae, Spirulina/Chlorella powder or tablets and Spirulina.Chlorophyll given in a less concentrated form contributes however alsoto the accumulation of the PPAR/RXR heterodimer activator. Consequently,grass, grass silage, alfalfa (which contains more chlorophyll thangrass) and other natural feeds can be given, in combination with aproduct which has a higher content of the PPAR/RXR heterodimer activatorand/or the precursor thereof in order to achieve the minimum amountsrequired by the invention.

Non-ruminants can be given metabolites of chlorophyll, i.e. first ofall, phytol, which further metabolises into phytenic acid, phytanicacid, pristanic acid and TMTD. In view of the cost for producing it onan industrial scale, phytol is the preferred product to be given to thelivestock animals in the present economic conditions. The othercompounds are more expensive to produce per PPAR/RXR heterodimeractivator equivalent, but can also be used in the method according tothe invention. Possibly, use can be made of living organisms containinga relatively high level of these compounds, for feeding the livestock.On the other hand, chlorophyll can also be given to non-ruminantstogether with chemical or biological agents that are active todissociate the phytyl chain from its chlorophyll parent molecule.

Instead of administering the above compounds respectively in the alcoholand in the acid form, they can also be administered in the form of asalt, an ester or an amide since these compounds will be converted backto the alcohol or the acid form in the gastro-intestinal system.

More generally, different derivatives of the above compounds andmetabolites of phytol can be used provided they act as PPAR/RXRheterodimer activator or provided they are a precusor of such anactivator in the livestock animals. Such compounds can be selected fromthe group of compounds corresponding to the following formulas:CH₃—CR₁H—CH₂ CH₂—CH₂—CR₂H—CH₂—CH₂—CH₂—CR₃H—CH₂—CH₂—(CH₂)_(m)—R₄ andCH₃—CR₁H—CH₂—CH₂—CH₂—CR₂H—CH₂—CH₂—CH₂—CR₃H—R₅,

wherein:

each of R₁, R₂, R₃ and R₆ is either CH₃, C₂H₅ or C₃H₇;

m=0−2;

R₄=CH₂—CR₆═CH—CH₂OH (phytol);

CH₂—CR₆═CH—CHO (phytenal);

CH₂—CR₆═CH—COOH (phytenic acid);

CH₂—CR₆H—CH₂—COOH (phytanic acid);

CH₂—CR₆H—CHOH—COOH (2-hydroxyphytanic acid);

CH₂—CR₆H—CH₂—CH₂OH;

CH₂—CO—CH₂—COOH;

CH₂—CR₆H—COOH (pristanic acid);

CHOH₂—CR₆H—COOH (3-hydroxypristanic acid);

CH₂—CR₆H—CH₂—CH₂OH;

CH₂—CR₆H—CHO (pristanal);

CH═CR₆—COOH (2, 3 pristenic acid);

CO—CR₆H—COOH (3 keto pristanic acid);

CH₂—CHOH—CH₂OH;

CH₂—CO—COOH;

CH₂—COOH;

CH₂—CHO;

CH₂—CH₂OH;

CHOH—CH₂OH;

CH₂—O—CHO;

COOH (4,8,12-TMTD); or

CHO and

R₅═CH₂—COOH or

COOH,

or which are a salt, an ester or an amide thereof, in particularchlorophyll, prophyrin, and phospholipid and di- or triacylglycerylesters. The names between brackets are the names of the respectivecompounds when m=0 and R₁, R₂, R₃ and optionally R₆ is CH₃.

In the method according to the invention the product comprising thePPAR/RXR heterodimer activator or the precursor thereof is given in apredetermined minimum amount and for a period of time such that thePPAR/RXR heterodimer activator accumulates in the livestock animal andan increased level is obtained in the livestock product. The minimumamount of activator to be given over a period of at least three days isexpressed as a ratio of the amount feed dry matter ingested by thelivestock animals during that period. In order to exclude any effect ofthe molecular weight of the activator or precursor and in order toexclude the effect of any difference in the number of functionalactivator groups in the precursor, the amount of activator is furtherexpressed in milli-equivalents, more particularly in PPAR/RXRheterodimer activator milli-equivalents. One millimole of phytol, i.e.294 mg of phytol, thus corresponds to one meq phytol. For example, whena precursor is used such as a di- or a triglyceride containing two orthree phytanate groups, one mole corresponds to two or respectivelythree equivalents of the di- or the triglyceride.

When the livestock animals eat a total amount of F kg feed dry weightover said period of time, they should be made to ingest an amount of theproduct which contains at least 5×F meq, preferably at least 10×F meq,and more preferably at least 15×F meq of said PPAR/RXR heterodimeractivator and/or precursor thereof. When different activators and/orprecursors are used, the sum of the respective amounts of thesecompounds should be greater than the minimum amount, provided thedifferent compounds are available for the livestock animal, i.e.provided the compounds can be taken up and, if necessary, converted intothe PPAR/RXR dimer activator. When phytol is used, the above amountscorrespond to about 0.15, 0.3 and 0.45% of dry diet weight,respectively.

During said period of time, the product can be given one or severaltimes. Preferably, the product is given at least once a day and is morepreferably given with the feed of the livestock animals. The product canbe given separately from the feed but preferably it is mixed therewith.The present invention also provides a feed for livestock animals whichis composed to contain at least 5 meq/kg feed dry weight, preferably atleast 10 meq/kg feed dry weight, and more preferably at least 15 meq/kgfeed dry weight of the PPAR/RXR heterodimer activator and/or precursorthereof, preferably phytol. This feed can either be manufactured inadvance or the farmer can also prepare it by mixing a product containingthe PPAR/RXR heterodimer activator and/or precursor thereof with otherfeed constituents. Optionally, the product can also be administered viathe drinking fluids.

The product is preferably given in said amounts over more than oneperiod of at least three days or over one or more longer periods, moreparticularly over at least one period of at least one week, morepreferably over at least one period of at least two weeks so that itfurther accumulates in the livestock animal. When the livestock animalsare slaughtered to produce the livestock product, in particular skeletalmeat, the livestock animals are made to ingest the product preferablyfor at least three days during the last week before slaughtering. Ofcourse, the product can already been given before the last week and alsoduring the entire last week. During the last days, it can moreover begiven in an increased amount in order to achieve a maximum level in thelivestock product upon slaughtering.

Compared to the therapeutic amounts of phytol and phytanic acid, theamounts given in accordance with the present invention are relativelyhigh, and are, in particular, considerably higher than the amounts whichcan be achieved by feeding grass or even alfalfa to ruminants. For a pigof 80 kg having a daily dry feed intake of 2 kg, the amounts of 5×F meq,10×F meq and 15×F meq correspond to 37 mg, 74 mg and 111 mg/kg bodyweight, respectively. For a chicken of 2 kg having a daily dry feedintake of 0.1 kg, these amounts correspond even to 74 mg, 148 mg and 222mg/kg body weight, respectively. In order to achieve an even higheraccumulation of the PPAR/RXR heterodimer activator, the livestockanimals can be made to ingest, over said period of time, at least 25×Fmeq, preferably at least 35×F meq, more preferably at least 50×F meq andmost preferably at least 65×F meq of the PPAR/RXR heterodimer activaterand/or precursor thereof. When phytol is used, these amounts correspondto about 0.75, 1.0, 1.5 and 2.0% of dry diet weight, respectively.Preferably, the livestock animals are made to ingest, over said periodof time, less than 175×F meq, and more preferably less than 125×F meq ofthe PPAR/RXR heterodimer activater and/or precursor thereof.

By means of the method according to the invention, livestock productscan be produced having certain minimum levels of the PPAR/RXRheterodimer activator, in particular of phytanic acid, pristanic acidand/or TMTD, by giving the products containing this or these activatorsand/or precursors thereof in a sufficiently large amount and for asufficient long period of time.

In the present specification the level of the PPAR/RXR heterodimeractivator is expressed as a percentage of total FAME fatty acids. Thesetotal FAME fatty acids comprise those fatty acids with a linear chain ofat least 12 carbons and are measured by the so-called FAME technique,which is well known for the skilled person and wherein, first, fattyacid methyl esters are prepared which are, subsequently, analysed viagas chromatography. The FAME procedure used for determining the resultsobtained by the present invention was as follows. Lipids were extractedfrom the samples using a dissolving solution that is specific to eachsample type. Nonadecanoic acid (19:0) was added as an internal standard.The two-step methylation procedure consisted of using a basic reagentNaOH/methanol followed by an acid reagent HCI/methanol. The fatty acidmethyl esters (FAME) were analyzed by GC (HP 6890, Hewlett-Packard,Brussels, Belgium) using a CP-Sil88 column for FAME (100 m×250 μm×0.25μm) (Chrompack, Middelburg, The Netherlands). The GC conditions were asadapted to each sample type. Peaks were identified by comparison ofretention times with those of the corresponding standards (Sigma,Botnew, Belgium; Nu-Chek-Prep, Elysian, M N). Identification of thepeaks included fatty acids between 12:0 and 22:6 and 5 different CLAisomers and phytanic acid and pristanic acid.

The product can be given to non-ruminant mammals and to poultry(broilers) so that a level of said PPAR/RXR heterodimer activator of atleast 0.2%, preferably of at least 0.5% and more preferably of at least1.0% of total FAME fatty acids is achieved in said livestock product, inparticular, in skeletal meat of the livestock animals. The non-ruminantmammals are preferably non-rodents since it has been found thatnon-rodents, generally, do not show the peroxisome proliferation uponactivation of the PPAR/RXR heterodimer that is typical in laboratorymice.

When the product is given to poultry (layers) producing eggs as thelivestock product, the product is preferably given so that a level ofsaid PPAR/RXR heterodimer activator of at least 1%, preferably of atleast 3% and more preferably of at least 5% of total FAME fatty acid isachieved in egg yolk of said eggs.

When the product is given to ruminants producing skeletal meat as thelivestock product, the product is preferably given so that a level ofsaid PPAR/RXR heterodimer activator of at least 0.7%, preferably of atleast 0.9% and more preferably of at least 1.0% of total FAME fatty acidis achieved in skeletal meat of the livestock animals.

When the product is given to ruminants producing milk as the livestockproduct, the product is preferably given so that a level of saidPPAR/RXR heterodimer activator higher than 0.75%, preferably higher than1.0% and more preferably higher than 1.5% of total FAME fatty acid isachieved in milk of the livestock animals.

When the product is given to aquatic animals such as the aquatic animalsdefined in the main group 4 “Fish and fish products” of the Europcode 2version of Apr. 8, 1999, which are incorporated herein by way ofreference, used to produce the livestock product in aquaculture, theproduct is preferably given so that a level of said PPAR/RXR heterodimeractivator of at least 0.7%, preferably of at least 0.9% and morepreferably of at least 1.0% of total FAME fatty acid is achieved in thelivestock product.

The method according to the invention cannot only be applied toaccumulate the PPAR/RXR heterodimer activator in livestock products butit also enables to improve the carcass quality of livestock animals. Inparticular for pigs, it has been observed that, from a group of pigsthat were given phytol, a number of pigs did no longer gain weight butexhibited a carcass configured towards more lean mass.

Experiments have also shown that, for some kinds of livestock animals,the supplementation of the feed with the PPAR/RXR heterodimer activatoror the precursor thereof has, within a population of the same livestockanimals, a different effect on a certain parameter so that thepopulation can be split up into two groups. For chicken (broilers) ithas for example be observed that the feeding of phytol causes in onegroup of chicken a greater accumulation of phytanic acid than in theother group. A selection can thus be made for chicken showing thelargest accumulation of PhA. For pigs, it has on the other hand beenobserved that, within one population, there were two groups, namely onegroup which fails to gain weight when being made to ingest phytol whilstanother group gained weight to a comparable extend as a control group.When, as explained hereabove, an improved carcass quality is theproduction goal, one should continue the phytol administering to thegroup of pigs that do not gain weight whilst when only an accumulationof the PPAR/RXR heterodimer activator is the production goal, one shouldcontinue with the group of pigs which gained weight.

EXAMPLE 1 Broilers

ROSS 308 broiler chicks were raised, lege artis, on an ad libitum diet,containing phytol at 2% by weight of feed that, characteristically,contains about 10% of humidity. The chicks consumed an average of about0.1 kg dry weight of the feed per day. The phytol in the diet replaced2% of the soybean oil included in feeds formulated based on the INVENutritional Requirement standard formula for a grower feed (formula120). Please refer to the following tables for the feed formula and forits chemical composition. Broiler feed composition Composition (%) 300Corn 26.00 800 Wheat 28.70 1402 Fullfat soybeans, toated 17.00 1424Soybean meal 48 + 2 17.00 2815 Patatoprotein 2.20 4200 Soybean oil 2.004370 INVE fat 3.70 5100 Monocalciumphospate 0.97 5150 Limestone 0.875170 Salt 0.28 5173 Sodiumbicarbonate 0.27 5300 L-lysine 0.17 5301DL-Methionin 0.24 5303 L-threonine 0.05 6511 Sacox 12%* 0.05 84928 INVEBroiler 0.5% 0.50 Sum 100.00

Chemical composition of broiler feed Composition (g/kg) Dry matter 889Crude ash 81 Crude protein 212 Fat 106 Starch 344 Crude fibres 31 Ca 8.0Total P 5.4 Av. P 4.0 Ca/Av. P 2.0 Dig lysine poultry 11.0 Dig met/diglys 0.47 Dig met + cyst/dig lys 0.73 Dig thr/dig lys 0.65 Dig try/diglys 0.21 MEn broiler (kCal) 3021 MEn broiler (kJ) 12.6 MEn poultry(kCal) 3259 MEn poultry (kJ) 13.6

The animals were slaughtered after 42 days and their tissues sampled foranalysis.

During the feeding trial, there was no difference in mortality ormorbidity when compared with a group that received the standard broilerfeed without the phytol supplement. It was observed that the final bodyweight (2122 g vs. 1842 g), the feed conversion rate (1.818 vs. 2.120)and the ratio breast weight/total weight (15.9% vs. 14.4%) were roughlyone tenth less advantageous under the phytol supplementation diet, butstill well within acceptable zoo technical ranges.

The fatty acid analysis of breast meat showed that PhA reached anaverage level of 2.6% of total fatty acids. Noteworthy was also aserious drop in PUFA (polyunsaturated fatty acid) content that isexplained by the lack of 2% of soybean oil in the phytol supplementeddiet.

Closer inspection of the results revealed that the broilers in thetreatment group could be classified neatly into two subgroups accordingto the content of PhA in the breast meat, with values of one subgroupclustered around 1.9% and the values of the other subgroup clusteredaround 3.6%, almost double. This illustrates clearly the emergence of aheretofore silent phenotype under conditions that put the metabolicpathway of PhA under heavier loads. If the initial weight gain iscorrelated with this final PhA deposition reate, a selection is possibleby phenotype after a short feeding trial to continue the finishing withthose individual animals with the most effective phenotype.

EXAMPLE 2 Layers

48 week old ISABROWN layers were kept, lege artis, and fed ad libitum adiet containing phytol at 2% by feed weight. The layers consumed onaverage about 0.1 kg dry weight of the feed a day. The phytol replaced2% of soybean oil included an INVE layer formulation with the followingfeed composition. Layer feed composition Composition (%) 300 Corn 45.50800 Wheat 20.00 1402 Fullfat soybeans, toasted 22.00 4200 Soybean oil2.00 5100 Monocalciumphospate 0.77 5150 Limestone 2.20 5152 LimestoneSEM white 6.50 5170 Salt 0.23 5173 Sodiumbicarbonate 0.18 5301DL-Methionin 0.12 84928 INVE Broiler 0.5% 0.50 Sum 100.00

There was no difference in mortality nor morbidity in comparison with agroup fed a standard layer diet without phytol supplementation. Althoughthe daily egg mass was lower with the supplemented diet, the feedconversion rate remained zoo technically within acceptable ranges. Thisis shown in this table below: Laying Daily rate Egg weight egg mass ADFI(%) (g/a/d) (g/a/d) (g/a/d) FCR control 90.3 65.6 59.2 112.3 1.9 2%phytol fed 83.0 62.8 52.1 103.8 2.0

The quality of the eggs with respect to standard parameters for shellquality and color of the yolk did not change significantly except for aless reddish coloring of the yolk in the supplemented group. The fattyacid analysis of the egg yolk revealed that supplementing the diet with2% by weight phytol resulted in a deposit of 11.5% of total FAME fattyacids of the branched chain fatty acids PhA, mainly, and a trace of PrA.Surprisingly, it appeared that the PhA displaced almost exclusively themono unsaturated fatty acids.

EXAMPLE 3 Pork

Hybrid boars weighing in at about 80 kg were kept lege artis and fed astandard finishing granulated feed sprayed on with phytol at a level of2% of feed weight. The feed was formulated and produced by Schatteman inWetteren, Belgium and contained on average about 7% of humidity. Onspraying, the feed readily absorbed this oily substance. The boars werefed the phytol supplemented granulated feed ad libitum and consumed onaverage about 1.8 kg of this feed per day. After one month, the boarswere slaughtered. Tissue samples were taken and the carcass qualityassessed. The carcasses were further butchered in the usual fashion tochops, loins, sausages and the like and the meat quality of the primecuts was assessed.

During the finishing period no difference in feeding behavior or levelof activity was observed between the boars fed the usual diet and thosefed the phytol enriched feed. Also, no animals got sick or died duringthe entire period. At slaughter, the boars in the intervention groupcould be divided into two groups according to their slaughter weight: agroup which thrived and gained weight comparable to boars which hadreceived the standard diet (weight gain 13.1 vs 11.2 kg) and anothergroup which thrived but failed to gain weight. We presume that, as isusual in pig rearing, genetic variability accounts for thesedifferences. Obviously, in practice, one could introduce a feed trialfor a week and continue on with the supplemented diet only with thoseanimals that showed already a significant weight gain or select thoseprone to carcass fat to lean mass redistribution to increase the carcassquality. initial final quality chinese moisture weight weight % meattype-index class color loss control group 80000 91500 60.88 1.79 A1 2.500.045 81000 95000 57.61 2.25 A2 3.00 0.043 88000 99500 51.32 2.54 B22.50 0.085 79000 94500 59.42 2.07 A1 2.00 0.067 2% phytol group 8000093000 57.99 2.42 B2 2.50 0.067 82000 91500 56.38 1.93 A2 2.50 0.06580000 77500 58.89 2.3 A1 3.50 0.031 87500 83000 60.62 1.83 A1 2.50 0.039average control 82000 95125 57.31 2.16 2.50 0.060 average 2% phytol82375 86250 58.47 2.12 2.75 0.050 average gainers 81000 92250 57.19 2.182.50 0.066 average no-gainers 83750 80250 59.76 2.07 3.00 0.035

With respect to the quality of the carcasses and the meat, nosignificant differences were found with those fed the standard diet. Thequality was assessed objectively using the following parameters: % meaton the carcass, type-index, meat class, meat moisture, meat color, meattemperature and meat pH change. It was remarkable that the group thatfailed to gain weight produced top quality, lean and good muscledcarcasses (quality class A1). average average color control group 2%phytol group control 2% phytol L (avg) 53.83 51.65 54.60 57.65 54.0555.95 49.26 52.03 54.43 52.82 a (avg) 6.40 8.08 7.65 5.78 7.92 6.21 8.107.57 6.98 7.45 b (avg) 15.07 15.40 15.16 15.08 15.56 14.97 13.84 15.0915.18 14.87 40 minutes pH L carré 5.94 6.14 6.02 6.00 5.83 5.88 5.956.01 6.03 5.92 pH R carré 6.14 6.13 5.99 5.84 5.70 5.84 6.01 5.90 8.035.86 pH L ham 6.17 5.87 6.19 5.98 5.95 6.40 5.93 6.09 6.05 6.09 pH Hcarré 6.29 5.90 6.13 6.01 5.72 6.51 5.90 6.98 6.08 6.28 T L carré (° C.)37.80 38.90 40.70 37.80 39.60 40.20 38.70 39.00 38.83 39.38 T T carré (°C.) 37.80 39.70 40.60 37.60 38.10 39.80 39.00 39.40 38.93 39.08 24 hourspH L carré 5.30 5.27 5.16 5.21 5.18 5.19 5.33 5.18 5.24 5.22 pH R carré5.29 5.21 5.28 5.19 5.16 5.18 5.29 5.31 5.24 5.24 pH L ham 5.29 5.315.33 5.25 5.35 5.29 5.32 5.29 5.30 5.31 pH R carré 5.33 5.37 5.41 5.285.29 5.29 5.33 5.28 5.35 5.30

With respect to the further processing of the pork, there were nonoticeable differences in handling and transforming the meat.

With respect to the content of PhA and PrA in the pork meat, levelsaveraging 2.3% of total FAME fatty acids were found. It was alsoremarkable that the inclusion of these branched chain fatty acids didnot produce a significant shift in the remainder of the fatty acidprofile like towards less unsaturated fatty acids as is commonly foundin CLA supplementation experiments.

EXAMPLE 4 Shrimp

Tiger shrimp (Penaeus Monodon), weighing in at 0.7 g a piece, were keptlege artis and fed a diet containing phytol at 2% of pellet diet weightand this during 4 weeks. The feeds were extruded using a standard shrimpgrow out recipe as developed by INVE Technologies nv, Dendermonde,Belgium, where the phytol replaced 2% of soybean oil. The shrimp wereallocated 20 a piece in triplicate tanks of 500 liters. After a week ofacclimatization the shrimp were fed at a daily rate of about 15% ofbiomass weight. Wheat Flour 43.319 43.319 Fish Meal Standard 999 35.00035.000 Defatted Soya Flour 50 9.610 9.610 Shrimphead Meal 4.000 4.000Wheat Gluten 2.000 2.000 Soya Oil 2.000 0.000 Phytol 0.000 2.000 Squidmeal 1.000 1.000 Brewers Yeast 0.750 0.750 Lecithin 0.679 0.679 Fish Oil0.642 0.642 INVE Premix 1.000 1.000 100.0 100.0

Formula shrimp finishing Moisture 10.20 7.37 Crude Protein 38.00 39.53Crude Fibre 1.20 1.23 Crude Ash 8.02 8.35 Crude Fat after Hydrolysis8.80 8.37

Proximate Analysis (% in diet)

At the end of the feeding trials, there was no difference in survivalrate compared with a similar triplicate group fed the standard dietwithout phytol supplementation. The delay on growth in the supplementeddiet group was marked but still satisfactory from a zoo technical pointof view (2.05 g vs. 3.3 g). During the first two weeks of feeding, theconsumption of feeds in both groups was similar, although the growthrate differed already at about the same proportion. During the last twoweeks however, the supplemented diet group consumed considerably lessfeed (53.7 vs 66.5 g), thus partially correcting an initially lessattractive feed conversion ratio. Moreover, the shrimps used in thisexample were quite young, for more adult shrimp, the delay on growth isexpected to be even smaller.

Fatty acid analysis revealed that during that feeding period the shrimptissue had accumulated an average of 5.3% of TFA (total fatty acids) ofPhA. Also, the total fat content dropped with about a fifth, a potentialmarketing advantage.

CLA BIBLIOGRAPHY

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1. A non-therapeutic method for achieving an increased level of at leastone PPAR/RXR heterodimer activator in a livestock product for humanconsumption, in particular in skeletal meat, milk and/or eggs, in whichmethod livestock animals, used in agri- or aquaculture for producing thelivestock product, are made to ingest at least one product comprisingsaid PPAR/RXR heterodimer activator and/or a precursor thereof which ismetabolised by the livestock animals into said PPAR/RXR heterodimeractivator, over such a period of time and in such an amount that thePPAR/RXR heterodimer activator is accumulated in the livestock animal sothat said increased PPAR/RXR heterodimer activator level is achieved inthe livestock product, characterised in that said PPAR/RXR heterodimeractivator is phytanic acid, a metabolite of phytanic acid, a derivativeof phytanic acid or of said metabolite, or a combination thereof and, inorder to accumulate the PPAR/RXR heterodimer activator in the livestockanimal, a predetermined amount of said product is given to the livestockanimals over at least one period of at least three days, during whichthe livestock animals ingest a total amount of F kg feed dry weight,which predetermined amount of said product contains at least 5×F meq,preferably at least 10×F meq, and more preferably at least 15×F meq ofsaid PPAR/RXR heterodimer activator and/or precursor thereof.
 2. Amethod according to claim 1, characterised in that said productcomprises as said PPAR/RXR heterodimer activator or as said precursorthereof at least one compound selected from the group of compounds whichcorrespond to the following formulas:CH₃—CR₁H—CH₂—CH₂—CH₂—CR₂H—CH₂—CH₂—CH₂—CR₃H—CH₂—CH₂—(CH₂)_(m)—R₄ andCH₃—CR₁H—CH₂—CH₂—CH₂—CR₂H—CH₂—CH₂—CH₂—CR₃H—R₅, wherein: each of R₁, R₂,R₃ and R₆ is either CH₃, C₂H₅ or C₃H₇; m=0−2; R₄=CH₂—CR₆═CH—CH₂OH;CH₂—CR₆═CH—CHO; CH₂—CR₆═CH—CO₂OH; CH₂—CR₆H—CH₂—COOH; CH₂—CR₆H—CHOH—COOH;CH₂—CR₆H—CH₂—CH₂OH; CH₂—CO—CH₂—COOH; CH₂—CR₆H—COOH; CHOH₂—CR₆H—COOH;CH₂—CR₆H—CH₂—CH₂OH; CH₂—CR₆H—CHO; CH═CR₆—COOH; CO—CR₆H—COOH;CH₂—CHOH—CH₂OH; CH₂—CO—COOH; CH₂—COOH; CH₂—CHO; CH₂—CH₂OH; CHOH—CH₂OH;CH₂—O—CHO; COOH; or CHO and R₅=CH₂—COOH or COOH, or which are a salt, anester or an amide thereof, in particular chlorophyll, porphyrin, andphospholipid and di- or triacylglyceryl esters.
 3. A method according toclaim 2, characterised in that said product comprises as said PPAR/RXRheterodimer activator or as said precursor thereof at least one compoundselected from the group of compounds which correspond to the followingformulas:CH₃—CR₁H—CH₂—CH₂—CH₂—CR₂H—CH₂—CH₂—CH₂—CR₃H—CH₂—CH₂—(CH₂)_(m)—R₄ wherein:R₁, R₂, R₃ and R₆=CH₃; m=0; and R₄=CH₂—CR₆═CH—CH₂OH (phytol);CH₂—CR₆H—CH₂—COOH (phytanic acid); or CH₂—CR₆H—COOH (pristanic acid),COOH (4,8,12-TMTD); or which are a salt, an ester or an amide thereof,in particular chlorophyll.
 4. A method according claim 1, characterisedin that said PPAR/RXR heterodimer activator is phytanic acid, pristanicacid, TMTD (4,8,12-trimethyltridecanoic acid), a derivative of theseacids or a combination thereof, the PPAR/RXR heterodimer activator beingpreferably phytanic acid and/or pristanic acid.
 5. A method according toclaim 1 characterised in that said product comprises phytol.
 6. A methodaccording to claim 1 characterised in that the livestock animals areslaughtered to produce said livestock product, in particular to produceskeletal meat, and the livestock animals are made to ingest said productfor at least three days during the last week before the slaughtering. 7.A method according to claim 1 characterised in that the livestockanimals are non-ruminant mammals or poultry, said product being given tothe livestock animals so that a level of said PPAR/RXR heterodimeractivator of at least 0.2%, preferably of at least 0.5% and morepreferably of at least 1.0% of total FAME fatty acids (comprising alinear chain of at least 12 carbon atoms) is achieved in said livestockproduct, in particular in skeletal meat of the livestock animals, thenon-ruminant mammals being preferably non-rodents.
 8. A method accordingto claim 7, characterised in that said livestock animals are poultry andsaid livestock products eggs, said product being given to the livestockanimals so that a level of said PPAR/RXR heterodimer activator of atleast 1%, preferably of at least 3% and more preferably of at least 5%of total FAME fatty acid is achieved in egg yolk of said eggs.
 9. Amethod according to claim 1 characterised in that the livestock animalsare ruminants, said product being given to the livestock animals so thata level of said PPAR/RXR heterodimer activator of at least 0.7%,preferably of at least 0.9% and more preferably of at least 1.0% oftotal FAME fatty acid is achieved in skeletal meat of the livestockanimals.
 10. A method according to claim 1, characterised in that thelivestock animals are ruminants, said product being given to thelivestock animals so that a level of said PPAR/RXR heterodimer activatorhigher than 0.75%, preferably higher than 1.0% and more preferablyhigher than 1.5% of total FAME fatty acids is achieved in milk of thelivestock animals.
 11. A method according to claim 9 characterised inthat said product comprises chlorophyll in a concentration of at least0.25% by dry weight, preferably of at least 0.50% by dry weight and morepreferably of at least 0.75% by dry weight.
 12. A method according toclaim 1, characterised in that the livestock animals are aquatic animalsused to produce said livestock product in aquaculture, said productbeing given to the livestock animals so that a level of said PPAR/RXRheterodimer activator of at least 0.7%, preferably of at least 0.9% andmore preferably of at least 1.0% of total long chain fatty acids isachieved in said livestock product.
 13. A method according to claim 1,characterised in that said product is given at least once a day duringsaid period of at least three days, said product being preferably givenwith the feed of the livestock animals.
 14. A method according to claim1, characterised in that said predetermined amount of said productcontains at least 25×F meq., preferably at least 35×F meq., morepreferably at least 50×F meq., and most preferably at least 65×F meq ofsaid PPAR/RXR heterodimer activator and/or precursor thereof.
 15. Amethod according to claim 1, characterised in that said predeterminedamount of said product contains less than 175×F meq., and preferablyless than 125×F meq of said PPAR/RXR heterodimer activator and/orprecursor thereof.
 16. A method according to claim 1, characterised inthat for an initial trial period, during which the livestock animals aremade to ingest said product, a parameter influenced by the ingestion ofsaid product in at least a number of the individual livestock animals isdetermined and, after the initial trial period, the livestock animalsare split up into at least two groups based on a difference in effect ofsaid product on said parameter, the parameter which is determined beingpreferably the gain of weight and/or the feed intake of the individuallivestock animals.
 17. A method to supplement the human diet with aPPAR/RXR heterodimer activator, in which method livestock animals, usedin agri- or aquaculture for producing a livestock product for humanconsumption, are made to ingest at least one product comprising saidPPAR/RXR heterodimer activator and/or a precursor thereof which ismetabolised by the livestock animals into said PPAR/RXR heterodimeractivator, over such a period of time and in such an amount that thePPAR/RXR heterodimer activator is accumulated in the livestock animal sothat an increased PPAR/RXR heterodimer activator level is achieved inthe livestock product, characterised in that said PPAR/RXR heterodimeractivator is phytanic acid, a metabolite of phytanic acid, a derivativeof phytanic acid or of said metabolite, or a combination thereof and, inorder to accumulate the PPAR/RXR heterodimer activator in the livestockanimal, a predetermined amount of said product is given to the livestockanimals over at least one period of at least three days, during whichthe livestock animals ingest a total amount of F kg feed dry weight,which predetermined amount of said product contains at least 5×F meq,preferably at least 10×F meq, and more preferably at least 15×F meq ofsaid PPAR/RXR heterodimer activator and/or precursor thereof.
 18. Amethod for improving the quality of carcass and meat of livestockanimals, in particular of pigs, characterised in that the livestockanimals are made to ingest at least one product which comprises aPPAR/RXR heterodimer activator selected from the group consisting ofphytanic acid, metabolites of phytanic acid, and derivatives of phytanicacid and of said metabolite, and/or a precursor thereof which ismetabolised by the livestock animals into said PPAR/RXR heterodimeractivator, and, in order to achieve an improved skeletal meat quality, apredetermined amount of said product is given to the livestock animalsover at least one period of at least three days, during which thelivestock animals ingest a total amount of F kg feed dry weight, whichpredetermined amount of said product contains at least 5×F meq,preferably at least 10×F meq, and more preferably at least 15×F meq ofsaid PPAR/RXR heterodimer activator and/or precursor thereof.
 19. Amethod according to claim 18, characterised in that said productcomprises phytol.
 20. A livestock product for human consumption, inparticular a livestock product for human consumption obtainable by amethod according to claim 1, which live stock product comprises at leastone PPAR/RXR heterodimer activator selected from the group consisting ofphytanic acid, metabolites of phytanic acid and derivatives of phytanicacid and of said metabolites, characterised in that the livestockproduct comprising egg yolk of poultry eggs, which egg yolk has a levelof said PPAR/RXR heterodimer activator of at least 1%, preferably of atleast 3% and more preferably of at least 5% of total FAME fatty acids,the livestock product being in particular poultry eggs.
 21. A livestockproduct according to claim 20, characterised in that the livestockproduct comprises at least 0.5 kg egg yolk.
 22. A livestock product forhuman consumption, in particular a livestock product for humanconsumption obtainable by a method according to claim 1 which live stockproduct comprises at least one PPAR/RXR heterodimer activator selectedfrom the group consisting of phytanic acid, metabolites of phytanic acidand derivatives of phytanic acid and of said metabolites, characterisedin that the livestock product is skeletal meat of non-ruminant mammalsor poultry having a fat content of maximum 70% on dry weight basis and alevel of said PPAR/RXR heterodimer activator of at least 0.2%,preferably of at least 0.5% and more preferably of at least 1.0% oftotal FAME fatty acids.
 23. A livestock product for human consumption,in particular a livestock product for human consumption obtainable by amethod according to claim 1, which live stock product comprises at leastone PPAR/RXR heterodimer activator selected from the group consisting ofphytanic acid, metabolites of phytanic acid and derivatives of phytanicacid and of said metabolites, characterised in that the livestockproduct is skeletal meat of ruminants having a fat content of maximum70% on dry weight basis and having a level of said PPAR/RXR heterodimeractivator of at least 0.7%, preferably of at least 0.9% and morepreferably of at least 1.0% of total FAME fatty acids.
 24. A livestockproduct for human consumption, in particular a livestock product forhuman consumption obtainable by a method according to claim 1, whichlive stock product comprises at least one PPAR/RXR heterodimer activatorselected from the group consisting of phytanic acid, metabolites ofphytanic acid and derivatives of phytanic acid and of said metabolites,characterised in that the livestock product contains a mixture of milkof at least 8 ruminants having a level of said PPAR/RXR heterodimeractivator higher than 0.75%, preferably higher than 1.0% and morepreferably higher than 1.5% of total FAME fatty acids.
 25. A livestockproduct for human consumption, in particular a livestock product forhuman consumption obtainable by a method according to claim 1, whichlive stock product comprises at least one PPAR/RXR heterodimer activatorselected from the group consisting of phytanic acid, metabolites ofphytanic acid and derivatives of phytanic acid and of said metabolites,characterised in that the livestock product are aquatic animals, inparticular aquatic animals defined in the main group 4 “Fish and fishproducts” of the Europcode 2 version of Apr. 8, 1999, having a level ofsaid PPAR/RXR heterodimer activator of at least 4.0%, preferably of atleast 5.0%, more preferably of at least 6.0% and most preferably of atleast 8.0% of total FAME fatty acids.
 26. A feed for livestock animalsfor use in a method according to claim 1, characterised in that itcomprises a PPAR/RXR heterodimer activator selected from the groupconsisting of phytanic acid, metabolites of phytanic acid, andderivatives of phytanic acid and of said metabolite, and/or a precursorthereof which is metabolised by the livestock animals into said PPAR/RXRheterodimer activator, the feed being composed to contain at least 5meq/kg feed dry weight, preferably at least 10 meq/kg feed dry weight,and more preferably at least 15 meq/kg feed dry weight of said PPAR/RXRheterodimer activator and/or precursor thereof.
 27. A feed according toclaim 25, characterised in that it contains at least 5 meq/kg feed dryweight, preferably at least 10 meq/kg feed dry weight, and morepreferably at least 15 meq/kg feed dry weight of phytol.